Synthesis and evaluation of benzo[b]thiophene derivatives as inhibitors of alkaline phosphatases

被引：39
作者：
Li, Lina [1 ,2 ,3 ,4 ,5 ,6 ]
Chang, Lei [1 ,2 ,3 ,4 ,5 ]
Pellet-Rostaing, Stephane [1 ,2 ,3 ,4 ,5 ]
Liger, Francois [1 ,2 ,3 ,4 ,5 ]
Lemaire, Marc [1 ,2 ,3 ,4 ,5 ]
Buchet, Rene [1 ,2 ,3 ,4 ,5 ]
Wu, Yuqing [6 ]
机构：
[1] Univ Lyon, F-69622 Villeurbanne, France
[2] Univ Lyon 1, F-69622 Villeurbanne, France
[3] Inst Natl Sci Appl, F-69621 Villeurbanne, France
[4] CPE Lyon, F-69616 Villeurbanne, France
[5] CNRS, UMR 5246, ICBMS, F-69622 Villeurbanne, France
[6] Jilin Univ, State Key Lab Supramol Struct & Mat, Changchun 130012, Peoples R China
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 20期
关键词：
Tetramisole; Benzo[b]thiophene; TNAP; Inhibitor; DIMETHYL-SULFOXIDE; MATRIX VESICLES; SYNOVIAL-FLUID; LEVAMISOLE; DEPOSITION; CRYSTALS; ANALOGS; TETRAMISOLE; CHEMISTRY; BINDING;
D O I：
10.1016/j.bmc.2009.08.048
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Presence of basic calcium phosphate in knee joints of osteoarthritis patients could be prevented by inhibiting tissue non-specific alkaline phosphatase (TNAP) activity. Levamisole or the L stereoisomer of tetramisole (a known TNAP inhibitor) has been used as a treatment for curing rheumatoid arthritis but its therapeutical use is limited due to side effects. We report the synthesis and the TNAP inhibition property of benzo[b] thiophene derivatives, among which benzothiopheno-tetramisole and benzothiopheno-2,3-dehydrotetramisole, which could be involved in a drug therapy for osteoarthritis. Two water soluble racemic benzothiopheno-tetramisole and -2,3-dehydrotetramisole with apparent inhibition constants K-i = 85 +/- 6 mu M and 135 +/- 3 mu M (n = 3) comparable to that of enantiomeric levamisole 93 +/- 4 mu M were found. Several novel derivatives showed more pronounced inhibition properties towards intestinal alkaline phosphatase than TNAP. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码：7290 / 7300
页数：11
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